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Achilles Therapeutics, a company built on the research of Crick group leader Charles Swanton and Sergio Quezada and Karl Peggs at the UCL Cancer Institute, has started a clinical trial for a new personalized immunotherapy for patients with melanoma.

The Phase I/II trial is testing a clonal neoantigen T cell (cNeT) therapy in around 20 patients with recurrent or metastatic melanoma. The first patient to take part in this trial has received treatment this week.

This new therapy uses a type of immune cell, called T lymphocytes, to target DNA mutations present in all cancer cells regardless of where they are in the body. This is possible as, while a cancer grows and mutates its DNA, all the cancer cells retain the earliest mutations present in the trunk of the tumor’s evolutionary tree, called clonal neoantigens that are presented to the immune system on the cancer cell surface. T Lymphocytes recognize these markers as a sign that they need to attack the cell.

The researchers will carefully select the particular lymphocytes used for each patient that recognize these clonal neoantigens that are unique to each person’s cancer. 

This is the first clinical trial to use personalized lymphocytes that can infiltrate tumors and target all cancer cells in a patient. 

“Cancer evolves over time in the body, developing various new mutations. This is one of the elements that makes it so hard to treat, as one tumor can be made up of many diverse cells which respond or are resistant to different treatments,” says Charles Swanton, group leader at the Crick and UCL and chief clinician at Cancer Research UK.

“That’s why these earliest mutations, present in all tumor cells, called clonal neoantigens are so important. We hope they will underpin a way to target all cancer cells and minimize the risk of treatment resistance.” 

The trial will evaluate the safety, tolerability and clinical effects of a single dose of cNeT, with initial findings due to be reported in the first half of 2021.

"I am delighted that we have dosed the very first patient in this exciting study which holds promise for patients with melanoma who have exhausted standard therapy options. The nature of this therapy is complex and operationally challenging and I am extremely proud of all those involved for achieving this especially in the current circumstances," says Samra Turajlic, National Chief Investigator of the study,Crick group leader and Consultant at the Royal Marsden NHS Foundation Trust.

The therapy has been developed based on findings from research as part of the TRACERx study, led by Charles and Sergio which identified the existence of clonal neoantigens.